甘露糖修饰甲氨蝶呤负载人血清白蛋白纳米颗粒的制备及配方优化

Title:Preparation and Formulation Optimization of Methotrexate-loaded Human Serum Albumin Nanoparticles Modified by Mannose

Volume: 28 Issue: 24

关键词: 甲氨蝶呤，纳米给药系统，中心复合设计，处方优化，MTXM- NPs，自身免疫性疾病。

摘要:

Background: Methotrexate (MTX) is the representative drug among the disease- modifying anti-rheumatic drugs. However, the conventional treatment with MTX showed many limitations and side effects.

Objective: To strengthen the targeting ability and circulation time of MTX in the treatment of rheumatoid arthritis, the present study focused on developing a novel drug delivery system of methotrexate-loaded human serum albumin nanoparticles (MTX-NPs) modified by mannose, which are referred to as MTX-M-NPs.

Methods: Firstly, mannose-derived carboxylic acid was synthesized and further modified on the surface of MTX-NPs to prepare MTX-M-NPs. The formulation of nanoparticles was optimized by the method of central composite design (CCD), with the drug lipid ratio, oil-aqueous ratio, and cholesterol or lecithin weight as the independent variables. The average particle size and encapsulation efficiency were the response variables. The response of different formulations was calculated, and the response surface diagram, contour diagram, and mathematical equation were used to relate the dependent and independent variables to predict the optimal formula ratio. The uptake of MTX-M-NPs by neutrophils was studied through confocal laser detection. Further, MTX-M-NPs were subjected to assessment of the pharmacokinetics profile after intravenous injection with Sprague-Dawley rats.

Results: This targeting drug delivery system was successfully developed. Results from Nuclear Magnetic Resonance and Fourier Transform Infrared Spectroscopy analysis can verify the successful preparation of this drug delivery system. Based on the optimized formula, MTX-M-NPs were prepared with a particle size of 188.17 ± 1.71 nm and an encapsulation rate of 95.55 ± 0.33%. MTX-M-NPs displayed significantly higher cellular uptake than MTX-NPs. The pharmacokinetic results showed that MTX-M-NPs could prolong the in vivo circulation time of MTX.

Conclusion: This targeting drug delivery system laid a promising foundation for the treatment of RA.

Cite this article as:

Preparation and Formulation Optimization of Methotrexate-loaded Human Serum Albumin Nanoparticles Modified by Mannose, Current Medicinal Chemistry 2021; 28 (24) . https://dx.doi.org/10.2174/0929867328666210118112640